Patients with uncontrolled epilepsy may have impairment of language and memory associated with their seizures. In addition, it is critical to map these functions when surgery is being considered. We are using imaging methods in an effort to replace more invasive approaches to detecting the effects of epilepsy on language and memory, and for preoperative mapping. Methods: We use positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to map language and memory in patients with temporal lobe epilepsy to perform non-invasive evaluation of functional cortex, and study the effect of epilepsy on cognitive anatomy in children and adults with seizures. Our studies in both normal volunteers and patients with uncontrolled seizures have shown that imaging evaluation compares well with more invasive procedures such as electrostimulation mapping and the intra-carotid sodium amytal test. We also evaluate the effect of seizures on the development of functional cognitive anatomy. [unreadable] [unreadable] Our previous studies have demonstrated that different fMRI paradigms may be used as probes of different aspects of language processing and that visual analysis is equivalent to quanitative region of interest analysis. We have examined patients deemed to have atypical language and find that fMRI demonstrates several patterns of atypical language processing that involve a distributed network in the left hemisphere and its right homologues. Activation outside there areas is rare, 80% of atypical language activation involves some form of regional activation. We have also examined the factors associated with language re-organization and find them associated with early age seizure onset, atypical handedness and remote cause. Patients with non-lesional neocortical epilepsy have a 30% incidence of atypical language, mesial temporal sclerosis 23%, tumor and focal dysplasia 14% each. All patients with a history of left hemisphere stroke have some form of language reorganization. [unreadable] [unreadable] fMRI language tasks reliably identify language areas but memory paradigms have been problematic. We examined an auditory description decision task for hippocampal activation and compared to IAT in 25 patients using a hippocampal mask analysis. We found that activation in hippocampus mostly reflected language dominance except where the hippocampus was sclerotic. We found poor correlation with IAT laterality indices, and only fair correlation between dominant HF activation and IAT memory capacity based on IAT. [unreadable] [unreadable] Arterial spin-labeled MRI is a new techniques that allows direct measurement of cerebral blood flow, as oppsoed to the indirect blood oxygenation level technique. this approqch may be less sensitive to perfusion limitations, nad provide more accurate data, particulalry in children. We have bene studying patients and normal volunteers in a comparions of ASL with the established 15-O water PET technique for cerebral blood flow estimation. PET was performed on a GE Signa 3T MRI scanner using a proximal inversion with a control for off resonance effects (PICORE)- quantitative imaging of perfusion using a single subtraction, second version (QUIPSS II) ASL sequence to estimate baseline flow. Images were corrected for subject motion. Flow values were averaged over 150 time points, in each temporal lobe. For 15O-PET, we used a GE (Waukesha, WI, USA) Advance Tomograph (FWHM = 6-7 mm), scanning 35 simultaneous slices with 4.25 mm slice separation. During scanning, in a quiet, dim room with eyes closed and ears unoccluded, a thermoplastic facemask held the subject s head in place. 10 mCi 15O-H2O was injected, and scanning performed for two minutes, using continuous arterial blood measurements with an automatic blood counter. Quantitative CBF values were obtained in regions drawn on co-registered structural MRI. For comparison with ASL-MRI, regional CBF from hippocampal formation, amygdala, parahippocampal gyrus, and fusiform gyrus were averaged. For both ASL-MRI and 15O-PET, an asymmetry index (AI) was derived using the formula: 2 * (ipsilateral-contralateral)/ (ipsilateral+contralateral).Our data suggest that ASL-MRI using QUIPSS II saturated pulse may be a useful tool for identifying temporal lobe epileptogenic zones, providing CBF data comparable to 15O-PET.[unreadable] [unreadable] fMRI language tasks reliably identify language areas in children and adults with localization related epilepsy Objective: To determine the relationship between structural lesions and atypical language representation in patients with left hemisphere epileptogenic zones. We studied 102 patients (mean age 22; range 4-55 years), using whole brain fMRI (EPI BOLD) with three language tasks using a block design: Verbal Fluency; Reading Comprehension, and Auditory Comprehension. fMRI t maps were rated visually. Results: fMRI showed left language dominance in 72 patients. Atypical language was found in 30 patients (29%). The incidence of atypical language varied with MRI type. Every patient (6/6) with a history of stroke, 36% (13/ 36) with normal MRI, 21% (6 /29) with mesial temporal sclerosis, 14% (4 /28) with focal cortical lesions (dysplasia, tumor, vascular malformation), and 33% (1/3) with Rasmussen?s Encephalitis had atypical language. Atypical language was more prevalent in patients with early seizure onset (43.2%, p<.05) and atypical handedness. Multivariate logistic regression analysis revealed that three clinical factors, handedness, seizure onset, and MRI type, accounted for a significant amount of the variance in language activation patterns. Early seizure onset was the strongest factor, followed by handedness. None of the three clinical factors were correlated with each other (p> .40). Patients with atypical language had lower verbal abilities (F = 6.96, p = .01) and a trend towards lower nonverbal abilities. Among patients with left hemisphere foci, fMRI language activation paradigms show atypical language in one third of patients with non lesional epilepsy, and one fifth of patients with MTS, but only one eighth of patients with small, discreet lesions. Early destructive processes involving substantial (but is size or location more important?) left hemisphere regions are most likely to lead to language re-organization. Early seizure onset, and atypical handedness, as well as the location and nature of pathological substrate, are important factors in language reorganization. [unreadable] [unreadable] Current Studies: After establishing and validation ASL with PET in adults we are embarking on fMRI rest and activation studies using arterial spin tagging at 3T that will examine developmental differences in cerebral blood flow and BOLD signal response. We also plan to study the effects of temporal lobectomy on the functional anatomy of language and working memory. Recent evidence suggests a central role for the anterior pole and the amygdala in these distributed neural systems. We will stuyd the role of anterior temporal lobe structures in modulating memory networks involved in semantic and affective processing. Using fMRI, patients with temporal lobe epilepsy (TLE) will be evaluated before and after anterior temporal lobectomy and behavioral results as well as fMRI activation patterns will be compared to those of age-,sex- and education-matched healthy controls. The study of the effects of a planned surgical lesion on cortical networks in humans has the potential to significantly contribute to the characterization of memory circuitry and can form the basis for the development of novel treatment strategies for patients with social and cognitive dysfunctions.